E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inflammatory Multiple Sclerosis |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of autologous PBSCT versus standard of care [i.e. Tysabri (natalizumab), Gilenya (fingolimod) or Tecfidera (dimethyl fumarate)] in patients with inflammatory MS failing alternate approved therapy.
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age between 18-55, inclusive 2. Diagnosis of MS using McDonald criteria of clinically definite MS 3. An EDSS of 2.0 to 6.0 4. Inflammatory disease despite treatment with standard disease modifying therapy including at least 6 months of interferon or copaxone. Inflammatory disease is defined based on both MRI (gadolinium enhancing lesions) and clinical activity (acute relapses *treated with IV or oral high dose corticosteroids and prescribed by a neurologist). Minimum disease activity required for failure is defined as: a) two or more *steroid treated clinical relapses with documented new objective signs on neurological examination documented by a neurologist and treated with steroids within the year prior to the study, or b) one *steroid treated clinical relapse within the year prior to study and evidence on MRI of active inflammation (i.e., gadolinium enhancement) within the last 12 months on an occasion separate from the clinical relapse (3 months before or after the clinical relapse). *A steroid treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, or a history of nonresponse to steroids, they were offered but not used. |
|
E.4 | Principal exclusion criteria |
1. Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy. 2. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis. 3. Positive pregnancy test 4. Inability or unwillingness to pursue effective means of birth control from the time of evaluation for eligibility until 6 months posttransplant (if on transplant) or until appropriate for nontransplant treatment (if on control arm). Effective birth control is defined as 1) abstinence defined as refraining from all acts of vaginal intercourse; 2) consistent use of birth control pills; 3) injectable birth control methods (Depoprovera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam. 5. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy 6. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary) 7. DLCO < 50% of predicted (for the transplant arm) 8. Resting LVEF < 50 % 9. Bilirubin > 2.0 mg/dl 10. Serum creatinine > 2.0 mg/dl 11. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications 12. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams 13. Diagnosis of primary progressive MS 14. Diagnosis of secondary progressive MS 15. Platelet count < 100,000/ul, WBC < 1,500 cells/mm3 16. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible 17. Active infection except asymptomatic bacteriuria 18. Use of natalizumab (Tysabri) within the previous 6 months 19. Use of fingolimod (Gilenya) within the previous 3 months 20. Use of Teriflunomide (Aubagio) within the previous 2 years unless cleared from the body (plasma concentration < 0.02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days 21. Prior treatment with CAMPATH (alemtuzumab) 22. Prior treatment with mitoxantrone 23. Any hereditary neurological disease such as CharcotMarieTooth disease (CMT) or Spinocerebellar ataxia (SCA) are contraindications 24. Use of tecfidera within the previous 3 months |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Disease progression, defined as a 1-point increase in the EDSS on consecutive evaluations at least 6 months apart and not due to a non-MS disease process. Patients will be followed for 5 years after randomization. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The last follow-up visit for the last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 1 |